The Correlation of BRCA 1 Promoter Methylation and Clinicopathological Appearance in Breast Cancer

Sony Sugiharto, Muh. Nasrum Massi, Syariffudin Wahid, Andi Fachruddin Benyamin, Nurjati Chaerani Siregar, Upik Anderiani Miskad, William Hamdani, Mochammad Hatta, Ilhamjaya Patellongi, Rosdiana Natsir

Abstract


Breast cancer is one of the common cancers in the worldwide. Most of breast cancer are sporadic. BRCA1 expression levels are reduced or totally loss in sporadic breast cancer. BRCA1 promoter methylation as one of the mechanisms to inactivating its function. BRCA1 promoter methylation associated with triple negative breast cancer (TNBC), poor prognosis, high grade, negativity of estrogen receptor (ER), progesterone receptor (PR) and human epidermal growth factor receptor 2(HER2). This study aims are to examine prevalence and correlation between BRCA1 promoter methylation and clinicopathology appearance in Indonesian women breast cancer. Subject are women with primary breast cancer and their formalin-fixed paraffin -embedded (FFPE) tumor specimen retrieved.

DNA was isolated and subjected to methylation specific PCR(MSPCR). DNA was isolated from primary tumor of 113 samples. Median age at diagnosis was 48 years (with range 28-80 years). Most of them, 67(59,3%) are include in aged categories <50 years. Incidence BRCA promoter methylation was found 82,3% (93 of 113.) There is significant correlation with BRCA1 promoter methylation with age<50 years old (p-value = 0.038) and Luminal B subtype (p-value = 0.033). Conclusion: BRCA1 promoter methylation in Indonesian women higher than other nations, correlate with younger patient and Luminal B subtype.


Keywords


Breast cancer; BRCA1 promoter methylation; prognosis.

Full Text:

PDF

References


J. Ferlay et al., “Cancer incidence and mortality worldwide: sources, methods and major patterns in GLOBOCAN 2012,” Int. J. Cancer, vol. 136, no. 5, pp. E359-386, Mar. 2015.

M. Wahidin, R. Noviani, S. Hermawan, V. Andriani, A. Ardian, and H. Djarir, “Population-Based Cancer Registration in Indonesia,” Asian Pac. J. Cancer Prev., vol. 13, no. 4, pp. 1709–1710, Apr. 2012.

R. D. Kennedy, J. E. Quinn, P. B. Mullan, P. G. Johnston, and D. P. Harkin, “The Role of BRCA1 in the Cellular Response to Chemotherapy,” JNCI J. Natl. Cancer Inst., vol. 96, no. 22, pp. 1659–1668, Nov. 2004.

C. R. Mueller and C. D. Roskelley, “Regulation of BRCA1 expression and its relationship to sporadic breast cancer,” Breast Cancer Res., vol. 5, no. 1, pp. 45–52, 2003.

A. Catteau and J. R. Morris, “BRCA1 methylation: a significant role in tumour development?,” Semin. Cancer Biol., vol. 12, no. 5, pp. 359–371, Oct. 2002.

M. Esteller et al., “Promoter Hypermethylation and BRCA1 Inactivation in Sporadic Breast and Ovarian Tumors,” JNCI J. Natl. Cancer Inst., vol. 92, no. 7, pp. 564–569, Apr. 2000.

O. A. Stefansson et al., “CpG island hypermethylation of BRCA1 and loss of pRb as co-occurring events in basal/triple-negative breast cancer,” Epigenetics, vol. 6, no. 5, pp. 638–649, May 2011.

A. M. Dworkin, T. H.-M. Huang, and A. E. Toland, “Epigenetic alterations in the breast: Implications for breast cancer detection, prognosis and treatment,” Semin. Cancer Biol., vol. 19, no. 3, pp. 165–171, Jun. 2009.

L. Zhang and X. Long, “Association of BRCA1 promoter methylation with sporadic breast cancers: Evidence from 40 studies,” Sci. Rep., vol. 5, p. 17869, Dec. 2015.

A. Bal et al., “BRCA1-methylated sporadic breast cancers are BRCA-like in showing a basal phenotype and absence of ER expression,” Virchows Arch. Int. J. Pathol., vol. 461, no. 3, pp. 305–312, Sep. 2012.

Y. Xu et al., “Promoter methylation of BRCA1 in triple-negative breast cancer predicts sensitivity to adjuvant chemotherapy,” Ann. Oncol., vol. 24, no. 6, pp. 1498–1505, Jun. 2013.

P. Sharma et al., “The prognostic value of BRCA1 promoter methylation in early stage triple negative breast cancer,” J. Cancer Ther. Res., vol. 3, no. 2, pp. 1–11, Mar. 2014.

E. Honrado et al., “Immunohistochemical classification of non-BRCA1/2 tumors identifies different groups that demonstrate the heterogeneity of BRCAX families,” Mod. Pathol. Off. J. U. S. Can. Acad. Pathol. Inc, vol. 20, no. 12, pp. 1298–1306, Dec. 2007.

N. C. Hsu, Y.-F. Huang, K. K. Yokoyama, P.-Y. Chu, F.-M. Chen, and M.-F. Hou, “Methylation of BRCA1 promoter region is associated with unfavorable prognosis in women with early-stage breast cancer,” PloS One, vol. 8, no. 2, p. e56256, 2013.

X. Xu et al., “BRCA1 Promoter Methylation is Associated with Increased Mortality among Women with Breast Cancer,” Breast Cancer Res. Treat., vol. 115, no. 2, pp. 397–404, May 2009.

M. E. H. Hammond et al., “American Society of Clinical Oncology/College of American Pathologists Guideline Recommendations for Immunohistochemical Testing of Estrogen and Progesterone Receptors in Breast Cancer,” J. Clin. Oncol., vol. 28, no. 16, pp. 2784–2795, Jun. 2010.

A. C. Wolff et al., “Recommendations for human epidermal growth factor receptor 2 testing in breast cancer: American Society of Clinical Oncology/College of American Pathologists clinical practice guideline update,” J. Clin. Oncol. Off. J. Am. Soc. Clin. Oncol., vol. 31, no. 31, pp. 3997–4013, Nov. 2013.

A. Goldhirsch, W. C. Wood, A. S. Coates, R. D. Gelber, B. Thürlimann, and H.-J. Senn, “Strategies for subtypes—dealing with the diversity of breast cancer: highlights of the St Gallen International Expert Consensus on the Primary Therapy of Early Breast Cancer 2011,” Ann. Oncol., vol. 22, no. 8, pp. 1736–1747, Aug. 2011.

P. Porter, “‘Westernizing’ Women’s Risks? Breast Cancer in Lower-Income Countries,” N. Engl. J. Med., vol. 358, no. 3, pp. 213–216, Jan. 2008.

S. Solikhah, S. Promthet, N. Rakkapao, and C. P. Hurst, “Validation of an Indonesian Version of the Breast Cancer Awareness Scale (BCAS-I),” Asian Pac. J. Cancer Prev. APJCP, vol. 18, no. 2, pp. 515–522, 2017.

R. D. Nindrea, W. A. Harahap, T. Aryandono, and L. Lazuardi, “Association of BRCA1 Promoter Methylation with Breast Cancer in Asia: A Meta- Analysis,” Asian Pac. J. Cancer Prev. APJCP, vol. 19, no. 4, pp. 885–889, 2018.

V. Birgisdottir, O. A. Stefansson, S. K. Bodvarsdottir, H. Hilmarsdottir, J. G. Jonasson, and J. E. Eyfjord, “Epigenetic silencing and deletion of the BRCA1 gene in sporadic breast cancer,” Breast Cancer Res., vol. 8, no. 4, p. R38, 2006.

J. S. Lee et al., “A comparative study of Korean with Caucasian breast cancer reveals frequency of methylation in multiple genes correlates with breast cancer in young, ER, PR-negative breast cancer in Korean women,” Cancer Biol. Ther., vol. 6, no. 7, pp. 1114–1120, Jul. 2007.

J. Mehrotra et al., “Estrogen receptor/progesterone receptor-negative breast cancers of young African-American women have a higher frequency of methylation of multiple genes than those of Caucasian women,” Clin. Cancer Res. Off. J. Am. Assoc. Cancer Res., vol. 10, no. 6, pp. 2052–2057, Mar. 2004.

M. M. Hosny, N. A. Sabek, T. B. El-Abaseri, F. M. Hassan, and S. H. Farrag, “Promoter Methylation Status of Breast Cancer Susceptibility Gene 1 and 17 Beta Hydroxysteroid Dehydrogenase Type 1 Gene in Sporadic Breast Cancer Patients,” International Journal of Breast Cancer, 2016. [Online]. Available: https://www.hindawi.com/journals/ijbc/2016/9545241/. [Accessed: 27-Jul-2018].

A. A. Hashmi et al., “Prognostic parameters of luminal A and luminal B intrinsic breast cancer subtypes of Pakistani patients,” World J. Surg. Oncol., vol. 16, Jan. 2018.

L. A. Carey, “Directed Therapy of Subtypes of Triple-Negative Breast Cancer,” The Oncologist, vol. 16, no. Supplement 1, pp. 71–78, Jan. 2011.

Z. Li, P. Hu, J. Tu, and N. Yu, “Luminal B breast cancer: patterns of recurrence and clinical outcome,” Oncotarget, vol. 7, no. 40, pp. 65024–65033, Aug. 2016.

Prihantono, P., Hatta, M., Binekada, C., Sampepajung, D., Islam AA, and Nilawati Usman, A. Ki-67 expression by immunohistochemistry and quantitative real-time polymerase chain reaction as predictor of clinical response to neoadjuvant chemotherapy in locally advanced breast cancer. J Oncol. 2017: 6209849. doi: 10.1155/2017/6209849


Refbacks

  • There are currently no refbacks.


 

 
  
 

 

  


About IJSBAR | Privacy PolicyTerms & Conditions | Contact Us | DisclaimerFAQs 

IJSBAR is published by (GSSRR).